Clinical trials in patients with metastatic and locally advanced colorectal carcinoma performed by the Southwest Oncology and Gastrointestinal Tumor Study Groups are reviewed. Therapy of metastatic disease remains unsatisfactory, with new agents and biochemical modulation being studied at present. Adjuvant trials have demonstrated the need for randomization and the inclusion of control groups. Preliminary results are consistent with potential usefulness of a combined modality approach in rectal carcinoma patients (stages B2 and C), with no effects on survival and/or recurrences in colon cancer.